Splicing regulators and their targets. Four different genes are illustrated on the left. Genes (a), (b) and (c) have two different splicing isoforms each, as shown, while (d) is constitutively spliced. Exons are depicted by the outlined boxes and introns by the straight lines connecting them. The splicing regulators are depicted by the colored circles on the right, which bind to the correspondingly colored cis-regulatory elements (upright rectangles) in the exons and introns of the genes, promoting (+) or repressing (-) the use of adjacent splice sites. The white circle and white element represent unknown regulators and unidentified elements. Different combinations of regulators result in differently spliced transcripts, as represented by the zigzag lines joining exons. For example, regulator I regulates the exclusion of alternative exons in (a) and (c). Regulator II is required by regulator I, as indicated by the co-occurrences of their cis-elements in introns near exons in genes (a) and (c), but regulator II does not require regulator I, as in alternative 5' splice site choice in (b), or mutually exclusive skipping of the first regulated exon in (c). Binding of regulator III to its corresponding cis-element in (b) promotes the inclusion of an additional exon.